Probiotics mixture and taurine attenuate L-arginine-induced acute pancreatitis in rats: Impact on transient receptor potential vanilloid-1 (TRPV-1)/IL-33/NF-κB signaling and apoptosis.

Acute pancreatitis (AP) is an inflammatory disorder of acinar cells. It may develop into severe chronic pancreatitis with a significant mortality rate. The current study aimed to assess the therapeutic effect of a Lactobacillus (LAB) mixture against rat AP. Six groups were created including control, taurine (300 mg/kg; i.p.) for 7 days, LAB mixture for 7 days, L-arginine (2.5 g/kg; i.p.) 2 doses with 1 h interval on 1st day, L-arginine+taurine, and L-arginine+LAB. Serum amylase and lipase activities were measured. Pancreatic tissue was used for histopathological examination, oxidative stress biomarkers including malondialdehyde (MDA) and reduced glutathione (GSH), and inflammatory biomarkers including myeloperoxidase (MPO) and interleukin (IL)-33 assessment. qRT-PCR was used for transient receptor potential vanilloid-1 (TRPV-1) investigation and Western blot analysis for measuring nuclear factor kappa-B (NF-κBp65) and the apoptosis biomarker; caspase-3. Taurine and LAB reduced lipase and significantly ameliorated induced oxidative stress by normalizing MDA and GSH contents. They counteracted inflammation by reducing MPO, IL-33, NF-κBp65, and TRPV-1. In addition, taurine and LAB counteracted apoptosis as proved by reduced caspase-3 expression. Taken together, these findings indicate that taurine and the use LAB mixture can mitigate AP by L-arginine via influencing TRPV-1/IL-33/NF-κB signaling together with exhibiting potent antioxidant and anti-inflammatory effects.

Irinotecan-gut microbiota interactions and the capability of probiotics to mitigate Irinotecan-associated toxicity.

BACKGROUND: Irinotecan is a chemotherapeutic agent used to treat a variety of tumors, including colorectal cancer (CRC). In the intestine, it is transformed into SN-38 by gut microbial enzymes, which is responsible for its toxicity during excretion. OBJECTIVE: Our study highlights the impact of Irinotecan on gut microbiota composition and the role of probiotics in limiting Irinotecan-associated diarrhea and suppressing gut bacterial ß-glucuronidase enzymes. MATERIAL AND METHODS: To investigate the effect of Irinotecan on the gut microbiota composition, we applied 16S rRNA gene sequencing in three groups of stool samples from healthy individuals, colon cancer, and Irinotecan treated patients (n = 5/group). Furthermore, three Lactobacillus spp.; Lactiplantibacillus plantarum (L. plantarum), Lactobacillus acidophilus (L. acidophilus), Lacticaseibacillus rhamnosus (L. rhamnosus) were used in a single and mixed form to in-vitro explore the effect of probiotics on the expression of ß-glucuronidase gene from E. coli. Also, probiotics were introduced in single and mixed forms in groups of mice before the administration of Irinotecan, and their protective effects were explored by assessing the level of reactive oxidative species (ROS) as well as studying the concomitant intestinal inflammation and apoptosis. RESULTS: The gut microbiota was disturbed in individuals with colon cancer and after Irinotecan treatment. In the healthy group, Firmicutes were more abundant than Bacteriodetes, which was the opposite in the case of colon-cancer or Irinotecan treated groups. Actinobacteria and Verrucomicrobia were markedly present within the healthy group, while Cyanobacteria were noted in colon-cancer and the Irinotecan-treated groups. Enterobacteriaceae and genus Dialister were more abundant in the colon-cancer group than in other groups. The abundance of Veillonella, Clostridium, Butryicicoccus, and Prevotella were increased in Irinotecan-treated groups compared to other groups. Using Lactobacillus spp. mixture in mice models significantly relieved Irinotecan-induced diarrhea through the reduction of both ß-glucuronidase expression and ROS, in addition to guarding gut epithelium against microbial dysbiosis and proliferative crypt injury. CONCLUSIONS: Irinotecan-based chemotherapy altered intestinal microbiota. The gut microbiota participates greatly in determining both the efficacy and toxicity of chemotherapies, of which the toxicity of Irinotecan is caused by the bacterial ß-glucuronidase enzymes. The gut microbiota can now be aimed and modulated to promote efficacy and decrease the toxicity of chemotherapeutics. The used probiotic regimen in this study lowered mucositis, oxidative stress, cellular inflammation, and apoptotic cascade induction of Irinotecan.

Tunable femtosecond laser suppresses the proliferation of breast cancer in vitro.

Worldwide, the most frequently diagnosed cancer is female breast cancer, and it poses a serious global health threat. Traditional cancer therapies are associated with various side effects, so developing better therapies for breast cancer is necessary, such as laser therapy which could be a promising treatment option. The aim of the current study was to investigate the femtosecond laser irradiation effect on breast cancer using T47D cell line as an in vitro model. Cells were seeded at a density of 5 × 104 cells/well in 96-well plates and incubated overnight. After that, the cells were exposed to femtosecond laser irradiation at various wavelengths falling in the UV, visible, and IR ranges for 3, 5, or 10 min and at a constant power of 100 mW. Cell viability was measured directly and 24 h after femtosecond laser irradiation using MTT assay. When using different femtosecond laser irradiation parameters, especially the 380 and 400 nm femtosecond laser irradiation, there was significant inhibition of breast cancer cell growth, either directly or 24 h after femtosecond laser exposure. Also, 420 and 440 nm significantly affected the viability of the cells. It was also observed that increasing exposure time enhances the observed effect, so 10 min exposure time was the best time of exposure. However, 700, 720, 750, and 780 nm did not significantly affect the cells viability with different exposure times. It was possible to conclude from the aforementioned results that femtosecond laser irradiation exerted a significant anticancer effect against T47D cells. Consequently, the femtosecond laser could be used successfully for breast cancer management.

Preparation of zinc oxide nanoparticles using laser-ablation technique: Retinal epithelial cell (ARPE-19) biocompatibility and antimicrobial activity when activated with femtosecond laser.

The unusual physical, chemical, and biological features of nanoparticles have sparked considerable attention in the ophthalmological applications. This study reports the synthesis and characterization of zinc oxide nanoparticles (ZnONPs) using laser-ablation at 100 mJ with different ablation times. The synthesized ZnONPs were spherical with an average size of 10.2 nm or 9.8 nm for laser ablation times of 20 and 30 min, respectively. The ZnONPs were screened for their antimicrobial activity against ophthalmological bacteria, methicillin-resistant S. aureus (MRSA) and Pseudomonas aeruginosa. The significant decrease in bacterial growth was observed after treatment with ZnONPs in combination with 400 nm femtosecond laser irradiation. ZnONPs were investigated for their antioxidant activity and biocompatibility towards retinal epithelial cells (ARPE-19). ZnONPs showed moderate antioxidant and free radical scavenging activity. ZnONPs prepared with an ablation time of 20 min were safer and more biocompatible than those prepared with an ablation time of 30 min, which were toxic to ARPE-19 cells with LC50 (11.3 µg/mL) and LC90 (18.3 µg/mL). In this study, laser ablation technique was used to create ZnONPs, and it was proposed that ZnONPs could have laser-activated antimicrobial activity for ophthalmological applications.

Metabolomic profiling and antioxidant potential of three fungal endophytes derived from Artemisia annua and Medicago sativa.

In this work, three fungal endophytes identified as Aspergillus terreus (AFL, AFSt and AFR), were studied for their antioxidant potential. LC-MS-based metabolomics, followed by multivariate statistical analysis were then applied to comprehensively profile their extracts. The three fungal endophytes revealed interesting antioxidant potential, in particular, the strain isolated from the Artemisia annua leaves (AFL), which was rich in different types of phenolic metabolites. Additionally, all fungal-derived ethyl acetate extracts showed potent inhibition against the prooxidant xanthine oxidase. Multivariate analysis (PCA and PLS-DA) demonstrated a unique chemical fingerprint for each strain, where phenolics, coumarins, and polyketides were the discriminative metabolites of the three fungal strains. The present findings highlighted the power of metabolomics in the chemotaxonomical classification of closely related strains. It also asserted the role of fungal endophytes in the management of oxidative stress, particularly when they are utilized in the production of fermented food products.

The effect of femtosecond laser irradiation on the growth kinetics of Staphylococcus aureus: An in vitro study.

We investigated the effect of femtosecond laser irradiation on the growth kinetics of Staphylococcus aureus. In order to improve laser-based antimicrobial therapy and develop a clinically viable modality, various laser parameters such as laser light wavelength, laser power, exposure time, and energy density were studied. The INSPIRE HF100 laser system (Spectra Physics) provided the femtosecond laser light, which was pumped by a mode-locked femtosecond Ti: sapphire laser MAI TAI HP (Spectra Physics). The survival of the bacterial cells was monitored after irradiation by determination of growth rate using optical density, which is a rapid, simple, and reliable method. The growth rate of laser-exposed cultures was compared to control cultures. Fifteen minutes of exposure to femtosecond laser radiation with a wavelength of 390 nm and 400 nm at an average power of 50 mW was enough to significantly reduce bacterial viability, with a lag in the growth phase of 5 h longer than the control culture (P < 0.0001 by ANOVA and Tukey test).

Anti-Proliferative and Anti-Biofilm Potentials of Bacteriocins Produced by Non-Pathogenic Enterococcus sp.

The incidence of cancer is increasing worldwide; likewise, the emergence of antibiotic-resistant biofilm-forming pathogens has led to a tremendous increase in morbidity and mortality. This study aimed to evaluate the probiotic properties of bacteriocin-producing Enterococcus sp. with a focus on their anti-biofilm and anticancer activities. Three of 79 Enterococcus isolates (FM43, FM65, FM50) were identified as producers of broad-spectrum bioactive molecules and were molecularly characterized as Enterococcus faecium by 16S rRNA sequencing. Phenotypic and genotypic screening for potential virulence factors revealed no factors known to promote pathogenicity. Treatment with proteinase K resulted in diminished antimicrobial activity; PCR-based screening for bacteriocin genes suggested the presence of both entA and entB genes that encode enterocins A and B, respectively. Maximum antimicrobial activity was detected during the early stationary phase, while activity disappeared after 24 h in culture. Bacteriocins from these isolates were stable at high temperatures and over a wide range of pH. Interestingly, crude supernatants of Ent. faecium FM43 and Ent. faecium FM50 resulted in significant destruction (80% and 48%, respectively; P < 0.05) of Streptococcus mutans ATCC 25175-associated preformed biofilms. Moreover, in vitro cytotoxicity assays revealed that extracts from Ent. faecium isolates FM43, FM65, and FM50 inhibited Caco-2 cell proliferation by 76.9%, 70%, and 85.3%, respectively. Taken together, the multifunctional capabilities of the microbial-derived proteins identified in our study suggest potentially important roles as alternative treatments for biofilm-associated infections and cancer.

Exploring the Antimicrobial and Antitumor Potentials of Streptomyces sp. AGM12-1 Isolated from Egyptian Soil.

The occurrence of extensive antibiotics resistant bacteria increased the demands for mining out new sources of antimicrobial agents. Actinomycetes, especially Streptomyces sp. have grasped considerable attention worldwide due to production of many useful bioactive metabolites. In the present study, a total of 52 actinomycetes were isolated from agricultural soil samples in Beni-Suef, Egypt. All isolates were characterized based on colony morphology, mycelium coloration, and pigment diffusion. They were screened for their capabilities to show antimicrobial activities against different indicator microorganisms, and only 20 isolates have shown significant antimicrobial activities against at least one of the tested indicator microorganisms. The isolate AGM12-1 was active against all tested microorganisms and showed a marked antitumor activity with IC50 3.3 and 1.1 µg/ml against HCT-116 and HepG-2 cell lines respectively. It was genotypically characterized as Streptomyces sp. with the presence of PKS Π biosynthetic gene cluster. Mannitol, ammonium sulfate, pH 7, 2% inoculum size and incubation for 11 days at 30°C were the optimum conditions that used to maximize the production and hence allowed purification of one active antimicrobial compound to homogeneity using high performance liquid chromatography with a molecular mass of m/z 488.05. Nuclear magnetic resonance structural elucidation showed that this compound was a diketopiperazine derivative.

Design, Synthesis and Evaluation of Novel Phthalimide Derivatives as in Vitro Anti-Microbial, Anti-Oxidant and Anti-Inflammatory Agents.

Sixteen new phthalimide derivatives were synthesized and evaluated for their in vitro anti-microbial, anti-oxidant and anti-inflammatory activities. The cytotoxicity for all synthesized compounds was also determined in cancer cell lines and in normal human cells. None of the target derivatives had any cytotoxic activity. (ZE)-2-[4-(1-Hydrazono-ethyl) phenyl]isoindoline-1,3-dione (12) showed remarkable anti-microbial activity. Its activity against Bacillus subtilis was 133%, 106% and 88.8% when compared with the standard antibiotics ampicillin, cefotaxime and gentamicin, respectively. Compound 12 also showed its highest activities in Gram negative bacteria against Pseudomonas aeruginosa where the percentage activities were 75% and 57.6% when compared sequentially with the standard antibiotics cefotaxime and gentamicin. It was also found that the compounds 2-[4-(4-ethyl-3-methyl-5-thioxo-1,2,4-triazolidin-3-yl)phenyl]isoindoline-1,3-dione (13b) and 2-[4-(3-methyl-5-thioxo-4-phenyl-1,2,4-triazolidin-3-yl)phenyl]isoindoline-1,3-dione (13c) had anti-oxidant activity. 4-(N'-{1-[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-phenyl]-ethylidene}-hydrazino)-benzenesulfonamide (17c) showed the highest in vitro anti-inflammatory activity of the tested compounds (a decrease of 32%). To determine the mechanism of the anti-inflammatory activity of 17c, a docking study was carried out on the COX-2 enzyme. The results confirmed that 17c had a higher binding energy score (-17.89 kcal/mol) than that of the ligand celecoxib (-17.27 kcal/mol).